Relating molecular T cell-mediated rejection activity in kidney transplant biopsies to time and to histologic tubulitis and atrophy-fibrosis
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F23%3A00083945" target="_blank" >RIV/00023001:_____/23:00083945 - isvavai.cz</a>
Result on the web
<a href="https://journals.lww.com/transplantjournal/Fulltext/2023/05000/Relating_Molecular_T_Cell_mediated_Rejection.17.aspx" target="_blank" >https://journals.lww.com/transplantjournal/Fulltext/2023/05000/Relating_Molecular_T_Cell_mediated_Rejection.17.aspx</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1097/TP.0000000000004396" target="_blank" >10.1097/TP.0000000000004396</a>
Alternative languages
Result language
angličtina
Original language name
Relating molecular T cell-mediated rejection activity in kidney transplant biopsies to time and to histologic tubulitis and atrophy-fibrosis
Original language description
Background. We studied the variation in molecular T cell-mediated rejection (TCMR) activity in kidney transplant indication biopsies and its relationship with histologic lesions (particularly tubulitis and atrophy-fibrosis) and time posttransplant.Methods. We examined 175 kidney transplant biopsies with molecular TCMR as defined by archetypal analysis in the INTERCOMEX study ( #NCT01299168). TCMR activity was defined by a molecular classifier.Results. Archetypal analysis identified 2 TCMR classes, TCMR1 and TCMR2: TCMR1 had higher TCMR activity and more antibody-mediated rejection ("mixed") activity and arteritis but little hyalinosis, whereas TCMR2 had less TCMR activity but more atrophy-fibrosis. TCMR1 and TCMR2 had similar levels of molecular injury and tubulitis. Both TCMR1 and TCMR2 biopsies were uncommon after 2 y posttransplant and were rare after 10 y, particularly TCMR1. Within late TCMR biopsies, TCMR classifier activity and activity molecules such as IFNG fell progressively with time, but tubulitis and molecular injury were sustained. Atrophy-fibrosis was increased in TCMR biopsies, even in the first year posttransplant, and rose with time posttransplant. TCMR1 and TCMR2 both reduced graft survival, but in random forests, the strongest determinant of survival after biopsies with TCMR was molecular injury, not TCMR activity.Conclusions. TCMR varies in intensity but is always strongly related to molecular injury and atrophy-fibrosis, which ultimately explains its effect on survival. We hypothesize, based on the reciprocal relationship with hyalinosis, that the TCMR1-TCMR2 gradient reflects calcineurin inhibitor drug underexposure, whereas the time-dependent decline in TCMR activity and frequency after the first year reflects T-cell exhaustion.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30217 - Urology and nephrology
Result continuities
Project
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Continuities
N - Vyzkumna aktivita podporovana z neverejnych zdroju
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Transplantation
ISSN
0041-1337
e-ISSN
1534-6080
Volume of the periodical
107
Issue of the periodical within the volume
5
Country of publishing house
US - UNITED STATES
Number of pages
13
Pages from-to
1102-1114
UT code for WoS article
000978303100022
EID of the result in the Scopus database
2-s2.0-85153900423